SCIENTIFIC DIVISION OF TYSON NUTRACEUTICALS, INC.

Chemical Name: (S)-pyrrolidine-2-carboxylic acid

Molecular Weight:115.1

Structrual Formula:

Nitrogen Content: 12.17%

Proline (13, 117)

L-Proline is a major amino acid found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. It is also essential for the immune system, and for necessary balance of this formula. It is an essential component of collagen and is important for proper functioning of joints and tendons. L-Proline is extremely important for the proper functioning of joints and tendons. Helps maintain and strengthen heart muscles.

Formation of Proline (142)

1. Proline is the only protein-forming amino acid with a secondary amino group. Proline is a non-essential amino acid synthesized from glutamic acid in 3 enzyme catalyzed steps.
2. Glutamate is phosphorilated on the gamma carbonyl to yield glutamyl phosphate by gamma-glutamyl to kinase. The glutamyl phosphate is reduced to glutamyl semialdehyde by gamma-glutamyl phosphate reductase.
3. This spontaneously cyclizes to form pyrroline carboxylate, which is reduced to proline in the final step of synthesis by pyrroline 5-carboxylate reductase.
4. Proline can also be synthesized from arginine in S. aureus via ornithine, which has the same carbon backbone as glutamyl semialdehyde with an amino group replacing the aldehyde.

Properties of Proline (13, 117)

Proline is hard to classify due to its ring structure, but it shares many properties of the aliphatic amino acids. Proline is unique among amino acids for several reasons. The most prominant is proline has the amino nitrogen cyclized with the side chain terminal carbon which leads to many of the unique properties of proline. This greatly restricts the conformational space available to the peptide in which proline occurs.

Other effects are a reduced barrier to cis-trans isomers of the peptide bond and a loss of H bonding capability of the immino nitrogen.
These effects give proline a unique role in secondary structure elements in which it occurs.
Proline also has other roles in structural proteins, signal transduction and other areas.
Proline is a component of collagen, a major structural component of cells and animals.
SH3(Src homology region 3) and WW domains of signal transduction pathway proteins recognize proline containing sequences and are used to mediate protein-protein interactions of signal transduction components.
Proline specific peptdases have been found that are sensitive to the conformation of proline. Cis-trans isomerization of proline is the rate limiting step in folding of some proteins and many cyclophilins or racemases catalyze the cis-trans racemizaton of proline containing proteins.

Metabolism of Proline (342)

Proline is a glycogenic amino acid. By L-Proline oxidase in the kidney, it is ring-opened and is oxidized to form L-Glutamic acid. L-Ornithine and L-Glutamic acid are converted to L-Proline via L-Glutamic acid-gamma-semialdehyde.
It is contained abundantly in collagen, and is intimately involved in the function of arthrosis and chordae.

Proline in Food

Proline can be found in eggs, dairy products and smaller amounts in meats and wheat germ.

Proline and Collagen (14, 343)

Collagen is the major structural protein found in tendons. ligaments, skin and bones. In the composition of collagen, it contains about 15 % proline. For the peptide sequence of collagen, it has the repetitve sequence Gly-X-Y where X and Y are frequently proline. It forms a three-stranded triple helix with each helix in a conformation similar to left-handed poly-proline II.
The prolines provide elasticity and strength due to the limited conformations proline can assume and the glycines are too close to the other strands of the helix to allow room for a side chain. The helix is held together by hydrogen bonds from the glycine NH to the carbonyl of residue Xaa of another strand.
Many of the prolines are hydroxylated at the 3 and 4 positions of the proline ring by prolyl hydroxylases that require vitamin C. This modification occurs before the collagen is folded into a three-stranded helix and the hydroxals stabilizes the helix by interchain hydrogen bonds.

Proline improves skin texture and aids collagen formation and helps contain the loss of collagen during aging. Also, collagen in the skin contains hydroxyproline and hydroxylysine, which is formed from proline and lysine, in which ascorbic acid seems to be important in this conversion. Collagen is the tough, elastic fibres of scar tissue, and the main structural component of tendons, ligaments and skin. Proline is therefore involved in tissue repair and wound healing.

Proline and reversing atherosclerotic deposits (345)

Proline is very important in the process of reversing atherosclerotic deposits. The therapeutic effect is two-fold:
First, proline helps to prevent the further build-up of atherosclerotic deposits.
second, proline helps to release already deposited fat globules from the blood vessel wall into the blood stream. When many fat globules are released from the plaques in the artery walls, the deposit size decreases, leading to a reversal of cardiovascular disease.

Proline and Vitamin C (12)

According to the current information available it would be recommended that an ample supply of vitamin C (ascorbic acid) be present to maximize the efficiency of proline.
Vitamin C deficiency will cause proline to be lost in the urine because of collagen breakdown. This is an early sign and precursor of degenerative disease.

Reference

• 13) Balch, James, MD, and Phyllis Balch, CNC, Prescription for Nutritional Healing, Avery Pub., 1997.
• 117) Cynober, L, editor, Amino Acid Metabolism & Therapy in Health & Nutritional Diseases, 1995.
• 342) Jaksi,T., Wagner, D.A., and Young, V.R. "Proline Metabolism in Adult Male Burn Patients and Healthy Control Subjects", Am. J. Clinical Nutrition, 1991.
• 343) Juva K. Hydroxylation of proline in the biosynthesis of collagen. An experimental study with chick embryo and granulation tissue of rat. Acta Physiol Scand Suppl. 1968;308:1-73.
• 14) Di Pasquale, M, Amino Acids and Proteins for the Athlete, the Anabolic Edge, 1997.
• 345) Pietzsch J, Bergmann R. Measurement of 5-hydroxy-2-aminovaleric acid as a specific marker of metal catalysed oxidation of proline and arginine residues of low density lipoprotein apolipoprotein B-100 in human atherosclerotic lesions. J Clin Pathol. 2003 Aug;56(8):622-3.
• 12) Latifi, Rifat, M.D., Amino Acids in Critical Care and Cancer, 1994.
• 341) Huq F., Thompson M, Ruell, P., "Changes in Serum Amino Acid Concentrations During Prolonged Endurance Running, J. Physiol., 1993.
• 340) Hiramatsu, T., Cortiell, J., Marchini, J.S. Chapman, T., Young, V.R., " Plasma Protein and Leucine Kinetics: Response to 4 Weeks With Proline-Free Diets in Young Adults", Am. J. Clinical Nutrition, 1994.